Improving outcomes for HIV-infected children in South Africa and Cote d'Ivoire

描述（由申请人提供）：及时诊断和治疗儿科艾滋病毒感染的计划在降低撒哈拉以南非洲儿童死亡率方面发挥着关键作用。临床领导者和政策制定者需要了解这些计划的长期效益和成本，这些计划在不同类型的艾滋病毒流行情况下可能会有所不同。南非是一个中等收入国家，艾滋病毒流行率非常高（30%：“普遍”艾滋病毒流行），感染艾滋病毒的妇女及其婴儿获得保健服务的机会非常好。科特迪瓦是一个低收入国家，艾滋病毒感染率较低（3%：“混合”艾滋病毒流行病），获得艾滋病毒相关卫生服务的机会更有限。这两个国家是撒哈拉以南非洲艾滋病毒流行的两个主要类型。 儿科艾滋病治疗的长期结果反映了数十年来的连续事件，因此无法使用传统方法（如临床试验或队列研究）进行充分研究。计算机模型可以通过预测短期和长期的生存和医疗资源利用率来为短期临床研究增加巨大价值;这可以帮助临床医生和政策制定者在有限资源的许多竞争需求中优先考虑。此外，计算机模型可以识别对生存和成本影响最大的因素，从而为未来的研究勾勒出关键的优先事项。 通过K 01 AI 078754和IMPAACT网络，NICHD，NIAID和NIMH支持了儿科HIV疾病的初步模型，预防艾滋病并发症的成本效益（CEPAC）-儿科模型。我们组建了一个具有儿科艾滋病毒、模拟建模和流行病学专业知识的国际研究小组，我们使用CEPAC-儿科模型对预防儿科艾滋病毒感染的策略进行分析，这些策略已为世卫组织的指导方针提供了信息。我们现在建议对CEPAC-Pediatric模型进行重大扩展，并使用我们的模型来评估诊断和治疗南非和科特迪瓦儿童HIV的新策略。我们的三个具体目标是：1）确定最有效和最有效的战略，为早期婴儿艾滋病毒 诊断; 2）调查儿童艾滋病毒治疗启动策略的临床结果和成本效益; 3）预测艾滋病毒感染儿童一线治疗监测和转为二线治疗策略的临床和经济结果。 这些分析反映了南非和科特迪瓦之间的关键比较，将反映非洲艾滋病毒流行的许多临床和经济状况。该项目降低艾滋病毒相关发病率和死亡率的目标与使命一致 NICHD：确保所有儿童都有机会充分发挥其潜力，过上健康和有所作为的生活，免受疾病或残疾之害。该项目还实现了艾滋病研究办公室、总统艾滋病紧急救援计划“拯救生命路线图”以及千年发展目标6和4的主要目标：优先开展针对妇女和弱势儿童的研究，确保儿童普遍获得艾滋病毒治疗，并降低全世界五岁以下儿童的死亡率。

DESCRIPTION (provided by applicant): Programs to promptly diagnose and treat pediatric HIV infection play a critical role in reducing childhood mortality in sub-Saharan Africa. Clinical leaders and policymakers need to understand the long-term benefits and costs of these programs, which may differ in settings with different types of HIV epidemics. South Africa is a middle-income country with a very high HIV prevalence (30%: a "generalized" HIV epidemic) and excellent access to health services for HIV-infected women and their infants. C¿te d'Ivoire is a low-income country with a lower HIV prevalence (3%: a "mixed" HIV epidemic) and more limited access to HIV-related health services. These two countries represent two of the key types of HIV epidemic in sub-Saharan Africa. The long-term outcomes of pediatric HIV treatment reflect a continuum of events over decades, and thus cannot be fully investigated using traditional methodologies, such as clinical trials or cohort studies. Computer models can add great value to shorter-term clinical studies by projecting survival and healthcare resource utilization over both short and long time horizons; this can assist clinicians and policymakers in prioritizing among many competing demands for limited resources. In addition, computer models can identify factors that will have the greatest influence on survival and costs, and thus outline critical priorities for future research. Through K01 AI078754 and the IMPAACT network, NICHD, NIAID, and NIMH have supported a preliminary model of pediatric HIV disease, the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model. We have assembled an international research team with expertise in pediatric HIV, simulation modeling, and epidemiology, and we have used the CEPAC-Pediatric model to conduct analyses of strategies to prevent pediatric HIV infection that have informed WHO guidelines. We now propose a major expansion of the CEPAC-Pediatric model and the use of our model to evaluate novel strategies to diagnose and treat pediatric HIV in South Africa and C¿te d'Ivoire. Our three specific aims are: 1) to determine the most effective and efficient strategies for early infant HIV diagnosis; 2) to investigate the clinical outcomes and cost- effectiveness of HIV treatment initiation strategies for children; and 3) to project the clinical and economic outcomes of strategies for monitoring 1st-line therapy and switching to 2nd-line therapy for HIV-infected children. By reflecting key comparisons between South Africa and C¿te d'Ivoire, these analyses will represent many of the clinical and economic conditions that characterize the HIV epidemic in Africa. The project's goals to reduce HIV-related morbidity and mortality align with the mission of NICHD: to ensure that all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability. The project further meets key goals of the Office of AIDS Research, the PEPFAR "Roadmap for Saving Lives," and Millennium Development Goals 6 and 4: to prioritize research for women and vulnerable children, to ensure universal access to HIV treatment for children, and to reduce under-five mortality worldwide.